Tissue fibrosis leads to fatal defunctionalization of tissues. For example, liver fibrosis leads to defunctionalization of the liver, and subsequently progresses to hepatocirrhosis or liver cancer, and pancreas fibrosis is commonly observed in cases of chronic pancreatitis or pancreatic cancer. Nevertheless, up to now, there have been no drugs for treating the fibrosis, and tissue grafting is the only effective cure. The reason that there are no drugs for treating the fibrosis is because molecular mechanism of tissue fibrosis has not been identified.
Recently, it has been found that tissue fibrosis is caused by activating stellate cells, which are one type of cell constituting tissues, and thus excessively expressing and accumulating an extracellular matrix such as collagen. It has been reported that the stellate cells become distributed in the pancreas, lungs, kidneys, and intestines, in addition to the liver.
The stellate cells play a key role in controlling retinoid homeostasis in the whole body. Vitamin A (retinol) acquired from diet is bound to retinol-binding protein (RBP) in blood flow; circulated, transferred to the stellate cells through STRA6 as a RBP receptor, and then stored as retinyl ester in cytoplasmic fat droplets. The present inventors disclosed that albumin that is expressed in the stellate cells and has intact fatty acid binding sites is involved in formation of vitamin A—containing fat droplets, inhibits activation of the stellate cells, and returns albumin expressed in the activated stellate cells to its previous state before activation (Non-Patent Document 1: Kim N, Yoo W, Lee J, Kim H, Lee H, Kim Y, Kim D, Oh J.* (2009) Formation of vitamin A fat droplets in pancreatic stellate cells requires albumin. Gut 58(10), 1382-90; Non-Patent Document 2: Kim N, Choi S, Lim C, Lee H, Oh J. (2010) Albumin mediates PPAR-g and C/EBP-a-induced phenotypic changes in pancreatic stellate cells. Biochem. Biophys. Res. Commun. 391(1), 640-44.)